Evidence map›Paper›PMID 19716475›Full record

ArticleChemistry & biology2009

Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD.

Leonardo Sorci, Yongping Pan, Yvonne Eyobo, Irina Rodionova, Nian Huang, Oleg Kurnasov, Shijun Zhong, Alexander D MacKerell, Hong Zhang, Andrei L Osterman

Open access · greenAbstract read
In one paragraph

Article in Chemistry & biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Inhibitors of NADInternational journal of molecular sciences · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Effect of Divalent Metal Ion on the Structure, Stability and Function ofInternational journal of molecular sciences · 2021
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Toward a structome of Acinetobacter baumannii drug targets.Protein science : a publication of the Protein Society · 2020
    Article
  16. Review
  17. Article
  18. TheProceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  19. Network-Based Metabolism-Centered Screening of Potential Drug Targets inFrontiers in cellular and infection microbiology · 2019
    Article
  20. The Journal of biological chemistry · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Leonardo SorciBurnham Institute for Medical Research, La Jolla, CA 92037, USA.
Yongping Pan
Yvonne Eyobo
Irina Rodionova
Nian Huang
Oleg Kurnasov
Shijun Zhong
Alexander D MacKerell
Hong Zhang
Andrei L Osterman
Sanford Burnham Prebys Medical Discovery Institute · USThe University of Texas Southwestern Medical Center · USUniversity of Maryland, Baltimore · US

Funding

Targeting cofactor biosynthesis in biodefense pathogensR01AI059146 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI OSTERMAN, ANDREI L · 2005 to 2009
$1.9M
NIAID NIH HHS AI059146NIAID NIH HHS R01 AI059146
6 · The paper itself

Abstract

The emergence of multidrug-resistant pathogens necessitates the search for new antibiotics acting on previously unexplored targets. Nicotinate mononucleotide adenylyltransferase of the NadD family, an essential enzyme of NAD biosynthesis in most bacteria, was selected as a target for structure-based inhibitor development. Using iterative in silico and in vitro screens, we identified small molecule compounds that efficiently inhibited target enzymes from Escherichia coli (ecNadD) and Bacillus anthracis (baNadD) but had no effect on functionally equivalent human enzymes. On-target antibacterial activity was demonstrated for some of the selected inhibitors. A 3D structure of baNadD was solved in complex with one of these inhibitors (3_02), providing mechanistic insights and guidelines for further improvement. Most importantly, the results of this study help validate NadD as a target for the development of antibacterial agents with potential broad-spectrum activity.

Indexed as

Anti-Bacterial AgentsBacillus anthracisBinding SitesComputational BiologyCrystallography, X-RayEnzyme InhibitorsEscherichia coliKineticsNADNicotinamide-Nucleotide AdenylyltransferaseProtein Structure, TertiaryAnti-Bacterial AgentsEnzyme InhibitorsNADNicotinamide-Nucleotide Adenylyltransferasenicotinic acid mononucleotide adenylyltransferase

Identifiers

PMID19716475
PMCPMC2770502
OpenAlexW2080335990

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.